PPM1D p.Cys478=
c.1434C>T · rs146477590 · VCV1600006
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.95%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.25 | GERP -3.8, phastCons 0.98 |
| Overall | ||
| CADD | 9.69 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.95%
South Asian · 1,773/91,086 alleles
Filtering AF
1.87%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.84%
Overall
0.124%
1,997/1,614,110 alleles · low-frequency
exomes 1,891/1,461,832 · genomes 106/152,278 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 1.95% | 51 |
| Remaining individualsnot grpmax-eligible | 0.166% | 601 |
| Middle Eastern | 0.115% | 866 |
| African / African-American | 0.0107% | 9,381 |
| European (non-Finnish) | 0.00831% | 12,041 |
| Admixed American | 0.00666% | 15,006 |
| Finnishnot grpmax-eligible | 0.00312% | 32,013 |
| East Asian | 0.00223% | 44,878 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- PPM1D
- Protein
- p.Cys478=
- Coding
- c.1434C>T
- MANE Select
- NM_003620
- dbSNP
- rs146477590
- Type
- single nucleotide variant
- Location
- chr17:60663168 (GRCh38)
- Gene constraint
- LOEUF 1.183 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 68.15 · 1 PDB
- Residue 478
- a UniProt-annotated variant site (in jdvs); a UniProt-annotated variant site (in oc; may be associated with disease susceptibility); a UniProt-annotated variant site (in bc; may be associated with disease susceptibility; gain-of-function mutation that results in increased negative regulation of p53 expression in response to ionizing radiation exposure); a UniProt-annotated variant site (in bc; may be associated with disease susceptibility)
Similar variants
- PPM1D p.Cys478Ter Conflicting classifications of pathogenicity ★ same residue
- PPM1D p.Cys478fs Likely pathogenic ★ same residue
- PPM1D p.Cys407Ter Pathogenic/Likely pathogenic ★★ same type
- PPM1D p.Gln404Ter Pathogenic ★★ same type
- PPM1D p.Gln462Ter Likely pathogenic ★★ same type
- PPM1D p.Glu423Ter Pathogenic ★★ same type
- PPM1D p.Ser421Ter Pathogenic/Likely pathogenic ★★ same type
- PPM1D p.Trp427Ter Pathogenic ★★ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ppm1d-p-cys478 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown